At the inception of the HNRC, the concept of HIV encephalitis had not been fully defined. Over the past 5 years it has become clear that HIV infection of the CNS is not an all-or-nothing phenomenon, rather there is a spectrum of severity of HIV infection within the CNS; but to define these changes requires sensitive quantitated histology that goes beyond traditional gross and light microscopic analysis, as well as regional estimation of viral burden. The central objectives of the Neuropathology Core are to delineate HIV and CMV related brain changes in a comprehensive fashion, and to relate anatomic findings and regional estimates of viral burden to antemortem neurobehavioral and imaging information. To achieve this, the Co-Pls, Drs. Wiley and masliah, will collaborate in the following studies; Dr. Masliah (Co-Pl of the UCSD site) will quantify neurologic damage on all deceased HNRC participants. The techniques include quantitative assessment of gliosis, morphometric quantitation of neuronal numbers in mid-frontal, superior temporal and inferior parietal cortex, laser confocal immunocytochemistry quantitation of synaptic density, and Golgi quantitation of synaptic spines in mid-frontal cortex. Dr. Wiley (Co-Pl of Pittsburgh site), will assess HIV CNS burden by performing semi-quantitative immunocytochemistry for HIV gp41 on cortical gray, white and deep gray matter of all autopsy cases, and quantitative PCR and HIV p24 antigen capture assays on CSF and CNS homogenates from the same regions. Together the quantitation of viral burden and CNS damage will provide the foundation for comparisons with neurobehavioral and neuroradiologic measurements of CNS disease.